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Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 127 records · Page 7Linked to original sources

Nitrite/nitrate (NOx) and sFas antigen levels in patients with multiple organ failure.

We assessed the plasma levels of nitrite/nitrate (NOx) and soluble Fas antigen (sFas) in patients with multiple organ failure (MOF). The NOx levels showed high levels in MOF patients with sepsis and without infection. A significant difference was not seen between the MOF patients complicated by sepsis and uncomplicated by infection, although the NOx levels in the former group tended to be higher. There was a significant correlation between NOx levels and sFas levels in MOF patients. Both sFas and NOx levels were high during MOF, and rapidly decreased when MOF was relieved. These findings suggest that sFas and NOx contribute to the development of MOF.

Humans↗

Changes in adhesion molecule levels in sepsis.

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1), CD11a, CD11b, CD18, endotoxin, and various inflammatory cytokines to clarify the relationship between adhesive molecules and cytokines in sepsis. We studied 21 patients with sepsis (sepsis group) and 13 patients with trauma not complicated by infection (trauma group). The mean sICAM-1 level was significantly higher in the sepsis group than in the trauma group. No significant difference was observed in the CD11a, CD11b, and CD18 levels between the two groups. The sICAM-1 levels significantly correlated with the levels of endotoxin, tumor necrosis factor alpha (TNF-alpha), and IL-8, but CD11a, CD11b, and CD18 levels did not correlate with endotoxin or cytokine levels. These findings suggest that ICAM-1 production is induced by endotoxins and cytokines produced in excess by inflammatory reactions and that endotoxins and cytokines are involved in qualitative, but not quantitative changes in LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18).

Adult↗

Nitrite/nitrate oxide (NOx) and cytokine levels in patients with septic shock.

To investigate the involvement of nitrite/nitrate oxide (NOx) in septic shock, and to evaluate the relationships between NOx and cytokines in patients with this disorder, we evaluated 11 patients with septic shock and 12 patients with sepsis unassociated with shock. NOx were measured with an automated system based on the Griess reaction. The plasma concentrations of various cytokines were determined by enzyme-linked immunosorbent assay. Endotoxin was determined by a specific assay after the plasma samples were processed by a perchloric acid method. The mean plasma levels of NOx in the group with shock significantly exceeded those in the group without shock. Significant correlations were observed between the plasma levels of NOx and those of endotoxin, tumor necrosis factor-alpha, and interleukin 8 in both groups. NOx appeared to be involved in the development of septic shock in humans. Endotoxin and cytokines appeared to be involved in the production of NOx.

Cytokines↗

Interleukin 11 levels in patients with disseminated intravascular coagulation.

We assessed the blood interleukin 11 (IL-11) levels in patients with disseminated intravascular coagulation (DIC). The IL-11 level exceeded the detection limit, i.e., IL-11 was positive, in 14 of the 21 patients in the group with DIC complicated by sepsis, with a mean value of 20.4 pg/ml. In the group with DIC uncomplicated by infection, IL-11 levels were above the detection limit in 8 of the 17 patients, and the average level was 10.6 pg/ml. The difference between the IL-11-positive rate in the two groups was not significant. Although IL-11 levels tended to be higher in the group with sepsis as a complication, the difference was not significant. The elevated IL-11 levels observed in patients with DIC, with or without complication by infection, seem quite appropriate as a biological response to increased platelets.

Adult↗

Plasma levels of interleukin-1 receptor antagonist (IL-1ra) and severity of illness in patients with burns.

The present study was conducted to determine whether a plasma interleukin-1 receptor antagonist (IL-1ra) would reflect the severity of burn injury and to examine the relation between IL-1ra and the cytokines. We studied 24 burn patients in whom the total burn surface area (TBSA) accounted for at least 20% of the body surface, and in whom serial blood samples could be obtained beginning immediately after the burn injury. Plasma levels of IL-1ra were determined by enzyme-linked immunosorbent assay (ELISA). Plasma levels of tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 were also determined by ELISA. Endotoxin was measured by an endotoxin-specific synthetic substrate method. There was a significant correlation between the plasma levels of IL-1ra and TBSA during the first week following burn injury. The IL-1ra level was the highest immediately after the burn injury. The level decreased markedly thereafter, and again rose when infection occurred. The IL-1ra level was extraordinarily elevated in patients who developed concomitant sepsis, septic shock or the septic multiple organ dysfunction syndrome. The IL-1ra level on admission and the maximum IL-1ra level during the observation period were significantly higher in the patients who eventually died than in the survivors. There was a significant correlation between the level of IL-1ra and that of TNF-alpha, IL-6 or IL-8 during the observation period. No correlation was found between IL-1ra and endotoxin. The plasma IL-1ra level was closely correlated with the severity of inflammation and the clinical status of the burn patients, regardless of the infection. Results suggest that IL-1ra can serve as an index of the systemic inflammatory response syndrome (SIRS).

Adult↗

[Cytokines in surgical stress].

The systemic inflammatory response is seen in association with various clinical conditions. Tumor necrosis factor, or other cytokines play an important role in systemic inflammatory response syndrome (SIRS). A frequent complication of SIRS is the development of organ system dysfunction, such as ARDS, DIC, renal failure, shock, and multiple organ dysfunction. Inflammatory cytokines become a trigger for the production of phospholipase A2, eicosnoids, NO, endothelin-1, thrombomodulin, polymorphonuclear leukocyte, and adhesion molecules. These mediators cause complex pathophysiologic condition in SIRS. In this study, we discuss a role of cytokines in surgical stress, hemorrhagic shock, burns, and septic shock.

Burns↗

Functional modification of vascular endothelial cells by cytokines during septic shock.

The function of vascular endothelial cells is to adjust blood vessel tonus, which contributes to maintaining homeostasis within blood vessels. However, inflammatory cytokines are produced in response to invasion by stimulating vascular endothelial cells and sometimes lead to shock or multiple organ failure. In the present study, we assessed cytokines in sepsis and septic shock, and various factors that are said to have a damaging effect on vascular endothelium. Endotoxin was measured by endotoxin-specific methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) were measured by enzyme-linked immunosorbent assay (ELISA). Endothelin-I was measured by radioimmunoassay (RIA). Nitric oxide was measured as metabolites of nitrite and nitrate oxides (NOx) by a method based on the Griess method. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF 1 alpha) were both measured by RIA. All of the factors except endotoxin were significantly higher in the septic shock group than in the non-shock group and significantly higher in the non-survivor group than in the survivor group. Significant correlations were also found between endothelin-1 and NOx and between TXB2 and PG1 alpha. Significant correlations were also found between TNF-alpha and IL-6, endothelin-1, NOx and TXB2, but no significant correlations were detected between any of them and endotoxin. In serious diseases such as septic shock, the vascular endothelial constricting factors, endothelin and TXB2, and the blood vessel relaxing factors NOx and PGF1 alpha increase almost simultaneously. This suggests that the body's regulating mechanisms are disrupted in these serious conditions. The results of this study also suggest that inflammatory cytokines may be involved in stimulating the production of these factors.

Adult↗

[Thoracoscopic enucleation for sclerosing hemangioma of the lung--a case report].

A 30-year-old female with sclerosing hemangioma of the lung (SHL) was managed by thoracoscopic enucleation. Under the left lateral decubitus position, four small skin incisions were made. The tumor, approximately 2.5 cm in diameter, was just under the pleura at the right S5, and was clearly demarcated without adhesions to mediastinal pleura. Because the tumor located near the hilum, a partial resection by intrathoracic Endo-GIA could not be performed. So the tumor was enucleated bluntly with an electrode knife being tugged by a tractive thread. After it was diagnosed as SHL by intraoperative imprint cytology, the stump was closed with running suture of 3-0 nylon. The patient was discharged on the 10th postoperative day without complication. No recurrence was found during a follow-up period of six months after the operation. Immunohistochemical findings suggested that the tumor cells were derived from type II pneumocytes. Thoracoscopic surgery appears to be a good indication for SHL which commonly occurs in young or middle-aged women and which is difficult to be diagnosed preoperatively. Thoracoscopic enucleation is considered to be a one of the safe methods especially for SHL which can not be resected by Endo-GIA.

Adult↗

Accumulation of immature CD3-CD4+CD8- single-positive cells that lack CD69 in epithelial cell tumors of the human thymus.

Human thymomas are epithelial tumors that are associated with a large number of nonneoplastic T cells of mainly immature phenotype, suggesting that epithelial cells of thymomas retain the function of thymic cortical epithelium. We report here that a large proportion (16-85%, mean +/- SD 58 +/- 22%, n = 17) of CD4+ single-positive T cells within the thymoma lack cell surface expression of CD3 and also of CD69, an early activation antigen that is expressed by positively selected thymocytes. Normal thymus had this CD4+CD8-CD3- population at much lower levels (12 +/- 7%, n = 11). It has been reported that in the human the CD4+CD8-CD3- cells are the predominant population that is intermediate between the CD4-CD8- double-negative and CD4+CD8+ double-positive stages. In contrast to CD4+ single-positive cells, most of the CD8+ single-positive cells in the thymoma as well as in the normal thymus expressed CD69 and a high level of CD3. A partial explanation of these observations is that the epithelial cells of thymoma were unable to positively select all the immature thymocytes generated in the thymoma. This relative inefficiency of positive selection could not be attributed solely to the paucity of MHC class II expression in the thymoma.

Antigens, CD↗

Portal and peripheral endotoxins in patients with esophageal varices undergoing surgery.

Under the hypothesis that portal endotoxemia, which has been considered evidence of endogenous endotoxemia, is actually a false-positive reaction of the Limulus test, the conventional method of determination, Toxicolor (TOX) and a new endotoxin-specific method, Endospecy (ES) were investigated, whereby portal endotoxemia was reexamined. Peripheral and portal blood samples were collected from 12 patients at various intervals during surgery for esophageal varices, and then evaluated by TOX and ES, the normal values of which are under 60.0 pg/ml and under 9.8 pg/ml, respectively. The mean peripheral and portal endotoxin (Et) levels by TOX were 23.1 pg/ml and 38.9 pg/ml, 1.5 h after the start of surgery, which continued to increase thereafter, the corresponding levels being 48.1 pg/ml and 58.7 pg/ml 8 h after the start of surgery, respectively. The portal Et levels were significantly higher by ES, indicating portal endotoxemia, the mean peripheral and portal Et levels being 6.9 pg/ml, and 6.5 pg/ml, 1.5 h after the start of surgery, these levels showing changes within a similar range. The levels determined by the conventional TOX method increased with time, to a portal Et level of 5.0 pg/ml 8 h after the start of surgery, whereas those determined by ES changed within the same range suggesting that the onset of portal endotoxemia primarily involves the G-factors and that endogenous endotoxemia does not occur.

Blood Specimen Collection↗

Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression.

The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm2 in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm2 (p < 0.00001). The significance of MVD was found in both node-negative and node-positive patients (p < 0.005 and p < 0.01, respectively). Multivariate analysis confirmed that MVD is an independent prognostic indicator for RFS. In the background factor analysis, MVD was significantly correlated with the number of metastatic nodes (p < 0.01). In addition, the immunocytochemical analysis for vascular endothelial growth factor (VEGF) demonstrated a close association between the increase in MVD and the expression of VEGF (p < 0.001). VEGF status also was a significant prognostic indicator in univariate analysis for RFS (p < 0.01). It was concluded that MVD is a potent prognostic indicator in primary breast cancer. Furthermore, it was also suggested that VEGF plays crucial roles in the promotion of angiogenesis in breast cancer.

Breast Neoplasms↗

Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery.

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg.kg-1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac function. Serum concentration of IL-8 in non-MP-treated patients (37 +/- 44 pg.ml-1 preoperatively) increased to 169 +/- 86 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 +/- 8.9 pg.ml-1 to 52 +/- 35 pg.ml-1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 +/- 30 pg.ml-1 to 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 +/- 15 pg.ml-1 to 135 +/- 85 pg.ml-1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 +/- 1.1 L.min-1.m-2) was higher than 2.3 +/- 0.8 L.min-1.m-2 of non MP-treated patients (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

Tumor necrosis factor production by human T-cells stimulated with bacterial superantigens.

Tumor necrosis factor (TNF) production from T-cells stimulated with superantigenic exotoxins, staphylococcal enterotoxin B and streptococcal pyrogenic exotoxin A was investigated in the presence of cells bearing distinct isotypes of HLA class II molecules. The main T-cell subset for TNF production was investigated in parallel. Similarly high levels of TNF production were induced upon stimulation with the toxins in the presence of DR+ or DQ+ cells, but only marginal levels of TNF production were induced in the presence of DP+ cells. Although both CD4+ T-cells and CD8+ T-cells produced TNF-alpha and TNF-beta in response to toxin stimulation in the presence of HLA class II+ cells, the former T-cell subset was the major source of producers of TNF-alpha and TNF-beta.

Bacterial Proteins↗

Plasma concentrations of type II phospholipase A2, cytokines and eicosanoids in patients with burns.

The plasma concentrations of type II phospholipase A2 (type II PLA2) and eicosanoids, such as leukotriene B4 (LTB4), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2), were determined by radioimmunoassay in 23 patients with burns covering at least 20 per cent of their body surface. Cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8) were determined by enzyme-immunosorbent assay. There was no increase in type II PLA2 concentration in the early stage of burns, but an increase in type II PLA2 concentration was triggered by infection (P < 0.0001). The level of type II PLA2 was significantly higher in the non-surviving group than in the surviving group (P = 0.0006), suggesting that it reflects the severity of the disease. There was a significant correlation between the maximum level of type II PLA2 and TNF-alpha (r = 0.6346, P = 0.0011). There was a significant correlation between the maximum level of type II PLA2 and the accompanying plasma concentrations of LTB4, 6-keto-PGF1 alpha, and TXB2 throughout the observation period (r = 0.4814, P = 0.0200; r = 0.5943, P = 0.0028; r = 0.4368, P = 0.0372 respectively). Plasma levels of LTB4, and TXB2 were significantly higher in the burn patients who died than in those who survived (P = 0.0493; P = 0.0493 respectively).

Adult↗

Mixed connective tissue disease complicated by pneumatosis cystoides intestinalis and malabsorption syndrome: case report and literature review.

A case of mixed connective tissue disease (MCTD) in a female with positive ribonucleoprotein antibody and overlapped manifestations of systemic lupus erythematosus and dermatomyositis is presented. During the last 9 years of her 13 year clinical course, she repeatedly manifested abdominal distension, pneumoperitoneum and malabsorption syndrome. She died, aged 54 years, of respiratory failure secondary to pulmonary compression from marked abdominal distention. Autopsy revealed esophageal fibrosis with ulceration and the typical appearance of pneumatosis cystoides intestinalis (PCI), in association with atrophy and fibrosis of the inner circular muscle layer of the small bowel. The association of PCI with MCTD is reviewed briefly.

Adult↗

CD68+ reactive histiocytosis complicating early gastric cancer.

A peculiar form of reactive, non-granulomatous proliferation of CD68+ histiocytes was demonstrated, for the first time, in the submucosal layer just beneath the IIa-type early gastric adenocarcinoma that focally invaded submucosal lymphatics. The histiocytic cells possessed plump eosinophilic and often foamy cytoplasm and eccentric small nuclei with apparent nucleoli. They contained periodic acid-Schiff-reactive granules, and were further immunoreactive for lysozyme and alpha 1-antitrypsin. The infiltration was ill-defined, and partly involved the tunica muscularis mucosae and the proper muscle layer. Markers of epithelial cells, Langerhans' histiocytes, smooth muscle cells and myofibroblasts were all negative.

Adenocarcinoma↗

Application of a new perchloric acid treatment method to measure endotoxin by an endotoxin-specific chromogenic Limulus test in neonatal septicemia.

The endotoxin in blood was measured to establish both the cut-off value and to detect Gram-negative septicemia. We employed a new perchloric acid treatment method using an endotoxin-specific chromogenic Limulus test (Endospecy test). The cut-off value of endotoxin in blood was 11.2 pg/mL. All cases of septicemia (n = 7) showed high values of endotoxin. Three cases were Group B streptococci, and two cases were Escherichia coli. The others were showed to be negative in blood cultures. The paired values of endotoxin titers during a 48 h interval were useful to evaluate the effectiveness of antibiotics.

Bacteremia↗

[Usefulness of endotoxin-specific limulus test for the measurement of endotoxin in cerebrospinal fluid in diagnosis of bacterial meningitis].

Using a new endotoxin-specific chromogneic limulus assay (Endoscopy test), endotoxin concentrations were measured in 93 specimens of cerebrospinal fluid (CSF) from 66 pediatric patients. Eighteen patients were diagnosed as having menigitios. Of these, 6 cases (group A) with gram-negative meningitis proven by culture had high CSF endotoxin concentrations of 115.3, (82-133) (median, range) pg/ml. Ten cases (group B) with gram-positive or aseptic meningitis had endotoxin concentrations of 2.15 (0.1-3.6) pg ml. Other 2 cases with bacterial meningitis (group C), in whom no pathogen was detected, had CSF endotoxin concentrations of more than 100 pg/ml. Four cases with encephalitis (group D) and 45 cases with non-meningitis or non- encephalitis (group E), had CSF endotoxin concentrations of less than 5 pg/ml. Despite a negative culture after antibiotic treatment in group A patients, endotoxin was cleared slowly from the CSF. A clearing of endotoxin from CSF was followed by alleviation of fever with a more gradual decline in CRP values. In 2 cases of group C, the negative bacterial culture appeared to be attributable to the previous treatment with antibiotics. However, these patients had high CSF endotoxin levels, indicating gram negative bacterial meningitis. In 17 CSF specimens from 5 patients of group A, in whom Haemophilus influenzae was detected on admission, an additional a latex agglutination test for the detection of H. influenzae polysaccharide antigen was performed. Only 3 specimens from 3 patients with CSF endotoxin concentrations of more than 80 pg/ml had a positive agglutination test. These results suggest that quantitation of endotoxin concentrations is useful for the diagnosis of gram-negative meningitis. And also, the clearance of endotoxin from CSF during treatment appears to be useful in determining the timing of when antibiotic should be stopped.

Adolescent↗